Evaluation of average bioequivalence of two oral formulations of amiodarone hydrochloride after single administration to healthy volunteers

Objective: To assess the average bioequivalence of two oral forms of amioda rone hydrochloride, amiodarone (Balkanpharma Co., Bulgaria) [test] and Cord arone((R)) (Sanofi, France) [reference] in healthy volunteers. Design: Single-dose, balanced, two-period, two-treatment, crossover study. Participants: 24 healthy Caucasian volunteers (12 men and 12 women) took pa rt in the study. Methods: Participants received single doses of amiodarone 400mg (2 x 200mg tablets) with a washout period of 30 days between treatments. Plasma sample s were taken at regular time intervals according to the study protocol for measuring plasma amiodarone and desethylamiodarone concentrations. The prim ary and secondary parameters area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)), maximum plasma concentration (C-m ax), time to reach maximum concentration (t(max)) and mean residence time ( MRT) were estimated. The point estimates (geometric means) of the test/refe rence ratio and the 90% confidence intervals (CIs) for the ratios of expect ed medians, assuming a multiplicative model, estimated by parametric and no nparametric analyses, were tested for inclusion in the defined bioequivalen ce range for the primary parameters. Results: The point estimates and the 90% CIs of the ratios of AUC(0-infinit y) and C-max after parametric analysis were 0.96 (0.87 to 1.06) and 1.02 (0 .86 to 1.21), respec tively. The two products were considered to be bioequi valent in their extent and rate of absorption. However, analysis of varianc e (ANOVA) revealed significant interindividual and between-period variabili ty in the primary parameters AUC(0-infinity), and C-max. Conclusions: The average extent and rate of absorption of the test and refe rence products containing amiodarone hydrochloride 200mg per tablet were no t significantly different. However, there was significant variability among individuals and between periods in AUC(0-infinity), and C-max Therefore, p rescribing the test product is appropriate, but switching between products is not recommended.